Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
Prenat Diagn ; 43(3): 288-293, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36738442

RESUMO

OBJECTIVE: To examine the impact of the fetal fraction (FF) on the screen-positive rate in screening for microdeletion 22q11.2. METHODS: This study is based on samples that were analyzed using the Harmony® Prenatal Test (Roche Inc). The study cohort comprised samples from women with singleton pregnancies who were at least 16 years old and at least at 11 weeks' gestation. Logistic regression analysis was used to determine significant covariates that carry an impact on the screen-positive rate. RESULTS: The study population consisted of 52,019 pregnancies, including 309 pregnancies with a high-risk result for microdeletion 22q11.2. Thus, the overall screen-positive rate was 0.59%. In the low-risk group, the FF was 10.1%, and in the high-risk group, it was 7.3%. Regression analysis indicated a strong correlation between the FF and the screen-positive rate. In the cases with an FF of <11.0%, the screen-positive rate was 0.92%, while it was 0.13% in the group with a higher FF. CONCLUSION: The screen-positive rate depends on the FF. In order to keep the rate low, we recommend restricting the analysis to samples with a FF of 11% and more.


Assuntos
Ácidos Nucleicos Livres , Gravidez , Humanos , Feminino , Adolescente , Diagnóstico Pré-Natal , Fatores de Risco , Feto , Idade Gestacional
2.
Prenat Diagn ; 41(10): 1258-1263, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32804406

RESUMO

OBJECTIVE: To examine the positive predictive value (PPV) of cfDNA screening for sex chromosome aneuploidies (SCA) in a large series of over 90 000 patients. METHODS: Retrospective study based on samples that were sent to Cenata, a private laboratory which uses the Harmony Prenatal Test. The SCA high-risk results were stratified according to the method of diagnostic testing and according to karyotype result. RESULTS: The study population consisted of 144 cases. The CfDNA test indicated monosomy X, XXX, XXY, and XYY in 62, 37, 40, and 5 cases, respectively. The overall PPV was 38.9% (30.9-47.4), 29.0% (18.2-42.9) for monosomy X, 29.7% (15.9-47.9) for 47,XXX, 57.5% (40.9-73.0) for 47,XXY, and 80.0% (28.4-99.5) for 47,XYY). A total of 112 (77.8%) women with a high-risk result for SCAs opted for prenatal karyotyping. In this group, there were significant differences in the PPV if the karyotype was assessed by amniocentesis or by CVS: 29.5% vs 50.0%. This significant difference was driven by the monosomy X result which shows a significantly higher PPV in CVS (54.6% (23.4-83.3) vs 17.1% (6.6-33.6)). For the other SCAs, the differences were not significant. CONCLUSION: PPV of an abnormal cfDNA test for SCAs is low, particularly for monosomy X. The confirmation rate depends on the type of confirmatory test.


Assuntos
Ácidos Nucleicos Livres/análise , Diagnóstico Pré-Natal/métodos , Aberrações dos Cromossomos Sexuais , Adulto , Ácidos Nucleicos Livres/sangue , Feminino , Alemanha , Humanos , Gravidez , Diagnóstico Pré-Natal/instrumentação , Diagnóstico Pré-Natal/tendências , Estudos Retrospectivos
3.
J Cell Sci ; 131(10)2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29661846

RESUMO

Tail-anchored (TA) proteins are anchored to their corresponding membrane via a single transmembrane segment (TMS) at their C-terminus. In yeast, the targeting of TA proteins to the endoplasmic reticulum (ER) can be mediated by the guided entry of TA proteins (GET) pathway, whereas it is not yet clear how mitochondrial TA proteins are targeted to their destination. It has been widely observed that some mitochondrial outer membrane (MOM) proteins are mistargeted to the ER when overexpressed or when their targeting signal is masked. However, the mechanism of this erroneous sorting is currently unknown. In this study, we demonstrate the involvement of the GET machinery in the mistargeting of suboptimal MOM proteins to the ER. These findings suggest that the GET machinery can, in principle, recognize and guide mitochondrial and non-canonical TA proteins. Hence, under normal conditions, an active mitochondrial targeting pathway must exist that dominates the kinetic competition against other pathways.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Adenosina Trifosfatases/metabolismo , Retículo Endoplasmático/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Retículo Endoplasmático/genética , Proteínas de Membrana/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Membranas Mitocondriais/metabolismo , Transporte Proteico , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
4.
EMBO Rep ; 17(7): 965-81, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27226123

RESUMO

Mitochondria are separated from the remainder of the eukaryotic cell by the mitochondrial outer membrane (MOM). The MOM plays an important role in different transport processes like lipid trafficking and protein import. In yeast, the ER-mitochondria encounter structure (ERMES) has a central, but poorly defined role in both activities. To understand the functions of the ERMES, we searched for suppressors of the deficiency of one of its components, Mdm10, and identified a novel mitochondrial protein that we named Mdm10 complementing protein 3 (Mcp3). Mcp3 partially rescues a variety of ERMES-related phenotypes. We further demonstrate that Mcp3 is an integral protein of the MOM that follows a unique import pathway. It is recognized initially by the import receptor Tom70 and then crosses the MOM via the translocase of the outer membrane. Mcp3 is next relayed to the TIM23 translocase at the inner membrane, gets processed by the inner membrane peptidase (IMP) and finally integrates into the MOM. Hence, Mcp3 follows a novel biogenesis route where a MOM protein is processed by a peptidase of the inner membrane.


Assuntos
Proteínas Fúngicas/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Peptídeo Hidrolases/metabolismo , Transdução de Sinais , Proteínas de Transporte/metabolismo , Proteínas Fúngicas/genética , Deleção de Genes , Dosagem de Genes , Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Complexos Multiproteicos , Transporte Proteico , Proteólise
5.
J Cell Sci ; 127(Pt 15): 3373-81, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24906800

RESUMO

Regulation of the localization of mRNAs and local translation are universal features in eukaryotes and contribute to cellular asymmetry and differentiation. In Saccharomyces cerevisiae, localization of mRNAs that encode membrane proteins requires the She protein machinery, including the RNA-binding protein She2p, as well as movement of the cortical endoplasmic reticulum (cER) to the yeast bud. In a screen for ER-specific proteins necessary for the directional transport of WSC2 and EAR1 mRNAs, we have identified enzymes that are involved in phospholipid metabolism. Loss of the phospholipid methyltransferase Cho2p, which showed the strongest impact on mRNA localization, disturbs mRNA localization, as well as ER morphology and segregation, owing to an increase in the amount of cellular phosphatidylethanolamine (PtdEtn). Mislocalized mRNPs containing She2p colocalize with aggregated cER structures, suggestive of the entrapment of mRNA and She2p by the elevated PtdEtn level. This was confirmed by the elevated binding of She2p to PtdEtn-containing liposomes. These findings underscore the importance of ER membrane integrity in mRNA transport.


Assuntos
Retículo Endoplasmático/metabolismo , Fosfatidiletanolamina N-Metiltransferase/metabolismo , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Metabolismo dos Lipídeos/genética , Lipossomos/metabolismo , Fosfatidiletanolamina N-Metiltransferase/genética , Fosfatidiletanolaminas/metabolismo , Ligação Proteica , Transporte Proteico , Transporte de RNA , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética
7.
FEBS Lett ; 592(19): 3210-3220, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30192984

RESUMO

Mitochondria are organelles containing two membranes that are distinct in composition and function. A role of the mitochondrial outer membrane (MOM) is to mediate contact of the organelle with the rest of the cell. In yeast, the MOM contains about 40 different integral proteins. Recently, we described the MOM protein Mcp3, which can serve as a multicopy suppressor of loss of ERMES complex that mediates mitochondria-endoplasmic reticulum contacts. To shed further light on the role of Mcp3 in the MOM, we analyzed its physical interaction with other proteins. We show that Mcp3 interacts with the MOM protein Om45 and the inner membrane protein Aim19. Our observations hint toward a potential involvement of Mcp3 in a structural and/or functional link between both mitochondrial membranes.


Assuntos
Proteínas de Membrana/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Mapas de Interação de Proteínas , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/genética , Mitocôndrias/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Mutação , Ligação Proteica , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA